Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 316, Issue 1, Pages H106-H112Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00561.2018
Keywords
blood vessel; exercise; immunofluorescence; shear stress
Funding
- American Heart Association (AHA) [17POST33670663]
- National Heart, Lung, and Blood Institute [P01-HL-091830]
- Veterans Affairs Rehabilitation Research & Development Service (VA RRD) Merit Grants [E6910-R, E1697-R]
- VA RR&D Small Projects in Rehabilitation Research (SPiRE) [R1433-P]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1-R01-DK-098646-01A1, R01-DK-099110]
- AHA [16GRNT30990018, 14SDG1850039, AHA16GRNT31050004]
- NIDDK [R01-DK-100505]
- VA BLR&D Merit Review Award [I01BX004133]
- VA RRD Grant [CDA-2 IK2RX001215]
- NIH [R03-AG-052848, R01-HL-141540]
- University of Utah (UU) Office of the Vice President for Research
- UU College of Health
- UU Center on Aging
- UU Diabetes and Metabolism Center
- Diabetes Research Center at Washington University in St. Louis [5-P30-DK-020579]
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Continuous laminar shear stress increases the process of autophagy, activates endothelial nitric oxide (NO) synthase phosphorylation at serine 1177 (p-eNOS(S1177)), and generates NO in bovine and human arterial endothelial cells (ECs) compared with static controls. However, the translational relevance of these findings has not been explored. In the current study, primary ECs were collected from the radial artery of 7 men using sterile J-wires before (Pre) and after (Post) 60 min of rhythmic handgrip exercise (HG) performed with the same arm. After ECs were identified by positive costaining for vascular endothelial cadherin and 4',6'-diamidino-2-phenylindole, immunofluorescent antibodies were used to assess indices of autophagy, NO generation, and superoxide anion (O-2 center dot(-)) production. Commercially available primary human arterial ECs were stained and processed in parallel to serve as controls. All end points were evaluated using 75 ECs from each subject. Relative to Pre-HG, HG elevated arterial shear rate (P < 0.05) similar to 3-fold, whereas heart rate, arterial pressure, and cardiac output were not altered. Compared with values obtained from ECs Pre-HG, Post-HG ECs displayed increased (P < 0.05) expression of p-eNOS(S1177), NO generation, O-2 center dot(-) production, BECLIN1, microtubule-associated proteins 1A/1B light chain 3B, autophagy-related gene 3, and lysosomal-associated membrane protein 2A and decreased (P < 0.05) expression (i.e., enhanced degradation) of the adaptor protein p62/sequestosome-1. These novel findings provide evidence that elevated arterial shear rate associated with functional hyperemia initiates autophagy, activates p-eNOS(S1177), and increases NO and O-2 center dot(-) generation in primary human ECs. NEW & NOTEWORTHY Previously, our group reported in bovine arterial and human arterial endothelial cells (ECs) that shear stress initiates trafficking of the autophagosome to the lysosome and increases endothelial nitric oxide (NO) synthase phosphorylation at serine 1177, NO generation, and O-2 center dot(-) production. Here, the translational relevance of these findings is documented. Specifically, functional hyperemia induced by rhythmic handgrip exercise elevates arterial shear rate to an extent that increases indices of autophagy, NO generation, and O-2 center dot(-) production in primary arterial ECs collected from healthy men.
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